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ASHP forecast 2022: challenges, opportunities amid ongoing pandemic
ASHP Foundation’s Pharmacy Forecast 2022:
Challenges, Opportunities Amid Ongoing Pandemic
By Karen Blum
Pharmacists will have plenty of opportunities to expand their scope of practice by pushing for provider status, assessing patients for social determinants of health (SDOH), helping in emergency pre- 0 paredness, managing drug shortages and demonstrating value through new service lines or business ventures, according to the ASHP Foundation’s Pharmacy Forecast for 2022.
The 10th edition of the forecast, presented at the ASHP 2021 Midyear Clinical Meeting and Exhibition, held virtually, and published in the American Journal of HealthSystem Pharmacy (2022;79[2]:23-51), surveyed 311 pharmacy leaders nationwide.
The 2022 report focused on five domains: delivering value to stakeholders; addressing access, disparities and equity; reimagining health systems for agility and resilience; building workforce capability; and honing pharmacy preparedness.
Access, Disparities and Equity
The COVID-19 pandemic pushed the need to address healthcare disparities and equity to the forefront, the authors said, with limited access to care highlighted by the initial rollout of vaccines. Pharmacists and pharmacy technicians are skilled and positioned to address SDOH and their effect on care access, and can work to improve population health. However, policy changes, such as adopting new payment models, are required to optimize pharmacists’ roles.
Pharmacists have had a long-standing role in public health, but only half of surveyed panelists indicated that pharmacists and pharmacy technicians will systematically screen patients for SDOH, said committee member Leyner Martinez, PharmD, MHA, the director of pharmacy services at Baptist Hospital of Miami. Adequate training is needed to expand services around these efforts, Dr. Martinez said.
However, 64% of panelists expect that standard measures will be developed and widely used to assess equity of care, and 87% of panelists predicted health systems will partner with community organizations to address healthcare disparities in their communities.
Regarding the use of technology, 73% of panelists said advanced data analytics will be used by health systems to address healthcare disparities, and 62% indicated that virtual assistant devices or healthcare mobile apps will allow patients to have access to a pharmacist for medication education and counseling. Meanwhile, 84% of panelists said the U.S. public health infrastructure would expand roles for pharmacists in preparedness planning, vaccine administration, screening for diseases and health coaching; and 78% said innovative scheduling and remote work solutions will be required to recruit and retain pharmacy team members.
As part of new legislation limiting surprise medical bills for patients, 63% of panelists said pharmacists will be required to advise patients on medication affordability and mediation assistance programs. In addition, 71% said payors will link value-based savings to improving health equity measures— another area where pharmacists can help lead initiatives, Dr. Martinez noted.
Overall, Dr. Martinez and her colleagues recommended that practice leaders support efforts for pharmacists to receive advanced independent provider status, and adopt analytical programs to assess and screen for SDOH to enhance medication management. Other recommendations include: • advocating that state and federal policy changes made during the pan-
demic be made a permanent part of the scope of pharmacy practice; • including pharmacists in transitions of care medication services; • allocating pharmacy labor resources to lead medication assistance program access and assist patients with medication affordability and adherence; and • collaborating with health plans and state agencies to continue establishing value-based care initiatives that include pharmacist-led comprehensive medication management services.
Agility and Resilience
“In our lifetime, the healthcare system has not faced this amount or duration of stress and challenges as we have over the last 22 months from the COVID-19 pandemic,” said Michelle Wiest, PharmD, BCPS, the vice president of pharmacy services for UC Health, in Cincinnati, while introducing the agility and resilience section. “Agility and resilience are paramount for health systems to be successful and to respond to patient care needs.”
Pharmacists demonstrated these capabilities during the public health emergency through methods such as evaluating emerging COVID-19 drug therapies to rapidly make patient care decisions, adjusting workflows to protect staff and preserve personal protective equipment, and managing numerous drug shortages. As such, 87% of panelists said health-system pharmacists will be essential providers in regional and national emergency preparedness response evaluation and planning.
Right-sizing staff based on unpredictable patient acuity loads and managing staff shortages and burnout also will play a role, panelists said, with 70% agreeing that pharmacy departments will maintain such contingency plans in at least 50% of hospitals.
In addition, most panelists said developing new models of care and services will be a performance expectation of health-system pharmacy leaders (Figure). Dr. Wiest and her colleagues recommend that pharmacy leaders urge health-system pharmacists to: • participate in local and national interdisciplinary public health teams;
• integrate technology and workforce Positive responses, % 100 80 60 40 20 81 Make the devel67 55 data to develop patient care models that optimize patient outcomes; and • engage in distribution relationships that encourage a stable pharmacy supply chain. They also said that pharmacists should become competent in the use of wearable health metric devices and invest in new opment of new models of patient care with pharmacists care models a performance as key providers of health services. expectation
Delivering Value
Figure. Key responses on agility Pharmacists will be called upon to demand resilience. onstrate value to stakeholders, including health systems, provider networks and payors, said Vivian Johnson, PharmD, MBA, the senior vice president of clinical services for Parkland Health and Hospital System, in Dallas. “Right now, we’re viewed as one of the most accessible professionals, because we are in the community,” she said. Some 92% of panelists said pharmacy leaders will add new service lines or business ventures to increase revenues, and 79% said the pharmacy department will significantly contribute to revenues. This could include greater pharmacist involvement in integrated practices, transitions of care, ambulatory care settings, hospital at-home programs or population health programs. Health-system pharmacies will be recognized as preferred sites of care for delivery of new complex therapies, according to 77% of panelists, and 94% said pharmacy departments will lead strategies to manage the financial impact of high-cost medications in 50% of health systems. Although 71% said health systems will invest in digital health solutions and artificial intelligence technology to improve medication management, Dr. Johnson said that number needs to be higher. “We need to continue pushing institutions to invest in technologies,” she said. “COVID-19 showed us ways in which we can provide care and medication management service without necessarily being at the bedside.” A copy of the full report is available at www.ashpfoundation.org/research/ pharmacy-forecast.
Collaborate with manufacturers on demand contracting, regional warehousing and other supply-chain surge strategies. Adapt specialty/other new pod structures
‘We need to continue pushing institutions to invest in technologies. COVID-19 showed us ways in which we can provide care and medication management service without necessarily being at the bedside.’ —Vivian Johnson, PharmD, MBA
The sources reported no relevant fi nancial disclosures.
Watch our video interviews about the forecast at
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INDICATIONS AND USE
Fentanyl Citrate Injection, for intravenous or intramuscular use, is indicated for: • Analgesic action of short duration during the anesthetic periods, premedication, induction and maintenance and in the immediate postoperative period (recovery room) as the need arises. • Use as an opioid analgesic supplement in general or regional anesthesia. • Administration with a neuroleptic as an anesthetic premedication, for the induction of anesthesia and as an adjunct in the maintenance of general and regional anesthesia. • Use as an anesthetic agent with oxygen in selected high risk patients, such as those undergoing open heart surgery or certain complicated neurological or orthopedic procedures. Fentanyl Citrate Injection should be administered only by persons specifically trained in the use of intravenous anesthetics and management of the respiratory effects of potent opioids. Ensure that an opioid antagonist, resuscitative and intubation equipment, and oxygen are readily available.
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF ADDICTION, ABUSE, AND MISUSE; LIFE- THREATENING RESPIRATORY DEPRESSION; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS See full prescribing information for complete boxed warning. • Fentanyl Citrate Injection exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient’s risk before prescribing and monitor regularly for these behaviors and conditions. • Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. • Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of fentanyl. • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.
Fentanyl Citrate Injection is contraindicated in patients with a hypersensitivity to fentanyl. Risks of Skeletal Muscle Rigidity and Skeletal Muscle Movement: Manage with neuromuscular blocking agent. See full prescribing information for more detail on managing these risks. Severe Cardiovascular Depression: Monitor during dosage initiation and titration. Serotonin Syndrome: Potentially life-threatening condition could result from concomitant serotonergic drug administration. Discontinue Fentanyl Citrate Injection if serotonin syndrome is suspected. Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, or Head Injury: Monitor for sedation and respiratory depression. The most common serious adverse reactions were respiratory depression, apnea, rigidity, and bradycardia.
To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC, at 1-800-551-7176 option 5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Concomitant Use of CNS Depressants: May decrease pulmonary arterial pressure and may cause hypotension. See full prescribing information for management instructions. For post-operative pain, start with the lowest effective dosage and monitor for potentiation of CNS depressant effects. Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: Avoid use with Fentanyl Citrate Injection because they may reduce the analgesic effect of Fentanyl Citrate Injection or precipitate withdrawal symptoms. Pregnancy: May cause fetal harm. Lactation: Infants exposed to Fentanyl Citrate Injection through breast milk should be monitored for excess sedation and respiratory depression. Geriatric Patients: Titrate slowly and monitor for CNS and respiratory depression.
This Important Safety Information does not include all the information needed to use Fentanyl Citrate Injection, safely and effectively. Please see full prescribing information, including Boxed Warning, for Fentanyl Citrate Injection at www.fresenius-kabi.com/us.
BRIEF SUMMARY OF PRESCRIBING INFORMATION This brief summary does not include all the information needed to use Fentanyl Citrate Injection safely and effectively. Please see full prescribing information including BOXED WARNING, for Fentanyl Citrate Injection, at www. fresenius-kabi.com/us. Fentanyl Citrate Injection, for intravenous or intramuscular use, CII WARNING: RISK OF ADDICTION, ABUSE, AND MISUSE; LIFETHREATENINGRESPIRATORY DEPRESSION; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse Fentanyl Citrate Injection exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing Fentanyl Citrate Injection, and monitor all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of Fentanyl Citrate Injection. Monitor for respiratory depression, especially during initiation of Fentanyl Citrate Injection or following a dose increase [see Warnings and Precautions]. Cytochrome P450 3A4 Interaction The concomitant use of Fentanyl Citrate Injection with all cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in fentanyl plasma concentration. Monitor patients receiving Fentanyl Citrate Injection and any CYP3A4 inhibitor or inducer [see Warnings and Precautions, Drug Interactions, Clinical Pharmacology] Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see Warnings and Precautions, Drug Interactions]. • Reserve concomitant prescribing of Fentanyl Citrate
Injection and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. • Limit dosages and durations to the minimum required. • Follow patients for signs and symptoms of respiratory depression and sedation. INDICATIONS AND USAGE
Fentanyl Citrate Injection is indicated for: • analgesic action of short duration during the anesthetic periods, premedication, induction and maintenance, and in the immediate postoperative period (recovery room) as the need arises. • use as a narcotic analgesic supplement in general or regional anesthesia. • administration with a neuroleptic as an anesthetic premedication, for the induction of anesthesia and as an adjunct in the maintenance of general and regional anesthesia. • use as an anesthetic agent with oxygen in selected high risk patients, such as those undergoing open heart surgery or certain complicated neurological or orthopedic procedures.
Important Dosage and Administration Instructions
Fentanyl Citrate Injection should be administered only by persons specifically trained in the use of intravenous anesthetics and management of the respiratory effects of potent opioids. • Ensure that an opioid antagonist, resuscitative and intubation equipment, and oxygen are readily available. • Individualize dosage based on factors such as age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used, and the surgical procedure involved. • Monitor vital signs routinely.
CONTRAINDICATIONS
Fentanyl Citrate Injection is contraindicated in patients with: • Hypersensitivity to fentanyl (e.g., anaphylaxis) [See Adverse
Reactions]
WARNINGS AND PRECAUTIONS [Also see Boxed Warning] Addiction, Abuse, and Misuse
Fentanyl Citrate Injection contains fentanyl, a Schedule II controlled substance. As an opioid, Fentanyl Citrate Injection exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence]. Opioids are sought by drug users and people with addiction disorders and are subject to criminal diversion. Consider these risks when handling Fentanyl Citrate Injection. Strategies to reduce these risks include proper product storage and control practices for a C-II drug. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal; respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Adequate facilities should be available for postoperative monitoring and ventilation of patients administered anesthetic doses of Fentanyl Citrate Injection. It is essential that these facilities be fully equipped to handle all degrees of respiratory depression. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage]. Carbon dioxide (CO2) retention from opioidinduced respiratory depression can exacerbate the sedating effects of opioids. To reduce the risk of respiratory depression, proper dosing and titration of Fentanyl Citrate Injection are essential. As with other potent opioids, the respiratory depressant effect of Fentanyl Citrate Injection may persist longer than the measured analgesic effect. The total dose of all opioid agonists administered should be considered by the practitioner before ordering opioid analgesics during recovery from anesthesia. Certain forms of conduction anesthesia, such as spinal anesthesia and some peridural anesthetics can alter respiration by blocking intercostal nerves. Through other mechanisms [see Clinical Pharmacology)] Fentanyl Citrate Injection can also alter respiration. Therefore, when Fentanyl Citrate Injection is used to supplement these forms of anesthesia, the anesthetist should be familiar with the physiological alterations involved, and be prepared to manage them in the patients selected for these forms of anesthesia. Patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of Fentanyl Citrate Injection. Elderly, cachectic, or debilitated patients may have altered pharmacokinetics or altered clearance compared to younger, healthier patients resulting in greater risk for respiratory depression. Monitor patients closely including vital signs, particularly when initiating and titrating Fentanyl Citrate Injection and when Fentanyl Citrate Injection is given concomitantly with other drugs that depress respiration. To reduce the risk of respiratory depression, proper dosing and titration of Fentanyl Citrate Injection are essential [see Dosage and Administration]. Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration].
Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers
Concomitant use of Fentanyl Citrate Injection with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of fentanyl and prolong opioid adverse reactions, which may exacerbate respiratory depression [see Warnings and Precautions], particularly when an inhibitor is added after a stable dose of Fentanyl Citrate Injection is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in Fentanyl Citrate Injectiontreated patients may increase fentanyl plasma concentrations and prolong opioid adverse reactions. When using Fentanyl Citrate Injection with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in Fentanyl Citrate Injection-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of Fentanyl Citrate Injection [see Dosage and Administration, Drug Interactions]. Concomitant use of Fentanyl Citrate Injection with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor, could result in lower than expected fentanyl plasma concentrations and, decrease efficacy. When using Fentanyl Citrate Injection with CYP3A4 inducers, or discontinuation of a CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the fentanyl Citrate Injection dosage [see Dosage and Administration, Drug Interactions].
Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants
When benzodiazepines or other CNS depressants are used with Fentanyl Citrate Injection, pulmonary arterial pressure may be decreased. This fact should be considered by those who conduct diagnostic and surgical procedures where interpretation of pulmonary arterial pressure measurements might determine final management of the patient. When high dose or anesthetic dosages of Fentanyl Citrate Injection are employed, even relatively small dosages of diazepam may cause cardiovascular depression. When Fentanyl Citrate Injection is used with CNS depressants, hypotension can occur. If it occurs, consider the possibility of hypovolemia and manage with appropriate parenteral fluid therapy. When operative conditions permit, consider repositioning the patient to improve venous return to the heart. Exercise care in moving and repositioning of patients because of the possibility of orthostatic hypotension. If volume expansion with fluids plus other countermeasures do not correct hypotension, consider administration of pressor agents other than epinephrine. Epinephrine may paradoxically decrease blood pressure in patients treated with a neuroleptic that blocks alpha adrenergic activity. Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Fentanyl Citrate Injection with benzodiazepines or other CNS depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). If the decision is made to manage postoperative pain with Fentanyl Citrate Injection concomitantly with a benzodiazepine or other CNS depressant, start dosing with the lowest effective dosage and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression, sedation, and hypotension. Fluids or other measures to counter hypotension should be available [see Drug Interactions].
Risks of Muscle Rigidity and Skeletal Muscle Movement
Fentanyl Citrate Injection may cause muscle rigidity, particularly involving the muscles of respiration. The incidence and severity of muscle rigidity is dose related. These effects are related to the dose and speed of injection. Skeletal muscle rigidity also has been reported to occur or recur infrequently in the extended postoperative period usually following high dose administration. In addition, skeletal muscle movements of various groups in the extremities, neck, and external eye have been reported during induction of anesthesia with Fentanyl Citrate Injection; these reported movements have, on rare occasions, been strong enough to pose patient management problems. These effects are related to the dose and speed of injection and its incidence can be reduced by: 1) administration of up to 1/4 of the full paralyzing dose of a non-depolarizing neuromuscular blocking agent just prior to administration of Fentanyl Citrate Injection; 2) administration of a full paralyzing dose of a neuromuscular blocking agent following loss of eyelash reflex when Fentanyl Citrate Injection is used in anesthetic doses titrated by slow intravenous infusion; or, 3) simultaneous administration of Fentanyl Citrate Injection and a full paralyzing dose of a neuromuscular blocking agent when Fentanyl Citrate Injection is used in rapidly administered anesthetic dosages. The neuromuscular blocking agent used should be compatible with the patient’s cardiovascular status.
Severe Cardiovascular Depression
Fentanyl Citrate Injection may cause severe bradycardia, severe hypotension including orthostatic hypotension, and syncope. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug Interactions]. In patients with circulatory shock,
Fentanyl Citrate Injection may cause vasodilation that can further reduce cardiac output and blood pressure. Monitor these patients for signs of hypotension after initiating or titrating the dosage of Fentanyl Citrate Injection.
Serotonin Syndrome with Concomitant Use of Serotonergic Drugs
Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of fentanyl with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazadone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) [see Drug Interactions]. This may occur within the recommended dosage range. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that. Discontinue Fentanyl Citrate Injection if serotonin syndrome is suspected.
Adrenal Insufficiency
Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.
Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, or Head Injury
In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), Fentanyl Citrate Injection may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of increasing intracranial pressure.
Risks of Use in Patients with Gastrointestinal Conditions
Fentanyl may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.
Increased Risks of Seizures in Patients with Seizure Disorders
Fentanyl may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical setting associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during Fentanyl Citrate Injection therapy.
Risks of Driving and Operating Machinery
Fentanyl Citrate Injection may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery after Fentanyl Citrate Injection administration.
Risks due to Interaction with Neuroleptic Agents
Many neuroleptic agents have been associated with QT prolongation, torsades de pointes, and cardiac arrest. Administer neuroleptic agents with extreme caution in the presence of risk factors for development of prolonged QT syndrome and torsades de pointes, such as: 1) clinically significant bradycardia (less than 50 bpm), 2) any clinically significant cardiac disease, including baseline prolonged QT interval, 3) treatment with Class I and Class III antiarrhythmics, 4) treatment with monoamine oxidase inhibitors (MAOI’s), 5) concomitant treatment with other drug products known to prolong the QT interval and 6) electrolyte imbalance, in particular hypokalemia and hypomagnesemia, or concomitant treatment with drugs (e.g. diuretics) that may cause electrolyte imbalance. Elevated blood pressure, with and without pre-existing hypertension, has been reported following administration of Fentanyl Citrate Injection combined with a neuroleptic. This might be due to unexplained alterations in sympathetic activity following large doses; however, it is also frequently attributed to anesthetic and surgical stimulation during light anesthesia. ECG monitoring is indicated when a neuroleptic agent is used in conjunction with Fentanyl Citrate Injection as an anesthetic premedication, for the induction of anesthesia, or as an adjunct in the maintenance of general or regional anesthesia. When fentanyl Citrate Injection is used with a neuroleptic and an EEG is used for postoperative monitoring, the EEG pattern may return to normal slowly.
ADVERSE REACTIONS
The following serious adverse reactions are described, or described in greater detail, in other sections: • Addiction, Abuse, and Misuse [see Warnings and Precautions] • Life-Threatening Respiratory Depression [see Warnings and Precautions] • Interactions with Benzodiazepines and Other CNS Depressants [see Warnings and Precautions] • Serotonin Syndrome [see Warnings and Precautions] • Severe Cardiovascular Depression [see Warnings and Precautions] • Gastrointestinal Adverse Reactions [see Warnings and
Precautions] • Seizures [see Warnings and Precautions] The following adverse reactions associated with the use of fentanyl were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. As with other opioid agonists, the most common serious adverse reactions reported to occur with fentanyl are respiratory depression, apnea, rigidity and bradycardia; if these remain untreated, respiratory arrest, circulatory depression or cardiac arrest could occur. Other adverse reactions that have been reported are hypertension, hypotension, dizziness, blurred vision, nausea, emesis, laryngospasm, diaphoresis, serotonin syndrome, adrenal insufficiency, and anaphylaxis. It has been reported that secondary rebound respiratory depression may occasionally occur postoperatively. When a tranquilizer is used with Fentanyl Citrate Injection, the following adverse reactions can occur: chills and/or shivering, restlessness and postoperative hallucinatory episodes (sometimes associated with transient periods of mental depression); extrapyramidal symptoms (dystonia, akathisia and oculogyric crisis) have been observed up to 24 hours postoperatively. When they occur, extrapyramidal symptoms can usually be controlled with anti-parkinson agents. Postoperative drowsiness is also frequently reported following the use of neuroleptics with fentanyl citrate. Cases of cardiac dysrhythmias, cardiac arrest, and death have been reported following the use of fentanyl citrate with a neuroleptic agent. Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Anaphylaxis: Anaphylaxis has been reported with ingredients contained in Fentanyl Citrate Injection Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see Clinical Pharmacology]. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS Clinically Significant Drug Interactions with Fentanyl Citrate Injection
Inhibitors of CYP3A4
Clinical Impact: The concomitant use of Fentanyl Citrate Injection and CYP3A4 inhibitors can increase the plasma concentration of fentanyl, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of Fentanyl Citrate Injection is achieved [see Warnings and Precautions]. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the fentanyl plasma concentration will decrease [see Clinical Pharmacology], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to fentanyl. Intervention: If concomitant use is necessary, consider dosage reduction of Fentanyl Citrate Injection until stable drug effects are achieved [see Dosage and Administration]. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the Fentanyl Citrate Injection dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir), grapefruit juice
CYP3A4 Inducers
Clinical Impact: The concomitant use of Fentanyl Citrate Injection and CYP3A4 inducers can decrease the plasma concentration of fentanyl [see Clinical Pharmacology], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to fentanyl [see Warnings and Precautions]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase [see Clinical Pharmacology], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. Intervention: If concomitant use is necessary, consider increasing the Fentanyl Citrate Injection dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider Fentanyl Citrate Injection dosage reduction and monitor for signs of respiratory depression. Examples: Rifampin, carbamazepine, phenytoin
Benzodiazepines and Other Central Nervous System (CNS) Depressants
Clinical Impact: The concomitant use of Fentanyl Citrate Injection with CNS depressants my result in decreased pulmonary artery pressure and may cause hypotension. Even small dosages of diazepam may cause cardiovascular depression when added to high dose or anesthetic dosages of Fentanyl Citrate Injection. As postoperative analgesia, concomitant use of Fentanyl Citrate Injection can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Intervention: As postoperative analgesia, start with a lower dose of Fentanyl Citrate Injection and monitor patients for signs of respiratory depression, sedation, and hypotension. Fluids or other measures to counter hypotension should be available [see Warnings and Precautions]. Examples: Benzodiazepines and other sedatives/ hypnotics, anxiolytics, barbiturates, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol.
Serotonergic Drugs
Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome [see Warnings and Precautions]. Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue Fentanyl Citrate Injection if serotonin syndrome is suspected.
Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Monoamine Oxidase Inhibitors
Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome [see Warnings and Precautions] or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions] Intervention: The use of Fentanyl Citrate Injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. Examples: Phenelzine, tranylcypromine, linezolid
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics
Clinical Impact: May reduce the analgesic effect of Fentanyl Citrate Injection and/or precipitate withdrawal symptoms. Intervention: Avoid concomitant use. Examples: Butorphanol, nalbuphine, pentazocine, buprenorphine.
Muscle Relaxants
Clinical Impact: Fentanyl may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of Fentanyl Citrate Injection and/or the muscle relaxant as necessary.
Diuretics
Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.
Anticholinergic Drugs
Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when Fentanyl Citrate Injection is used concomitantly with anticholinergic drugs.
Neuroleptics
Clinical Impact: Elevated blood pressure, with and without pre-existing hypertension, has been reported following administration of Fentanyl Citrate Injection combined with a neuroleptic [see Warnings and Precautions]. Intervention: ECG monitoring is indicated when a neuroleptic agent is used in conjunction with Fentanyl Citrate Injection as an anesthetic premedication, for the induction of anesthesia, or as an adjunct in the maintenance of general or regional anesthesia.
Nitrous oxide
Clinical Impact: Nitrous oxide has been reported to produce cardiovascular depression when given with higher doses of Fentanyl Citrate Injection. Intervention: Monitor patients for signs of cardiovascular depression that may be greater than otherwise expected.
USE IN SPECIFIC POPULATIONS Pregnancy
Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. Available data with Fentanyl Citrate Injection in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, fentanyl administration to pregnant rats during organogenesis was embryocidal at doses within the range of the human recommended dosing. No evidence of malformations was noted in animal studies completed to date [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly. Labor or Delivery There are insufficient data to support the use of fentanyl in labor or delivery. Therefore, such use is not recommended. Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid- induced respiratory depression in the neonate. Fentanyl Citrate Injection is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including Fentanyl Citrate Injection, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Data Animal Data Fentanyl has been shown to embryocidal in pregnant rats at doses of 30 mcg/kg intravenously (0.05 times the human dose of 100 mcg/kg on a mg/m2 basis) and 160 mcg/kg subcutaneously (0.26 times the human dose of 100 mcg/kg on a mg/m2 basis). There was no evidence of teratogenicity reported. No evidence of malformations or adverse effects on the fetus was reported in a published study in which pregnant rats were administered fentanyl continuously via subcutaneously implanted osmotic minipumps at doses of 10, 100, or 500 mcg/ kg/day starting 2-weeks prior to breeding and throughout pregnancy. The high dose was approximately 0.81 times the human dose of 100 mcg/kg on a mg/m2 basis.
Lactation
Risk Summary Fentanyl is present in breast milk. One published lactation study reports a relative infant dose of fentanyl of 0.38%. However, there is insufficient information to determine the effects of fentanyl on the breastfed infant and the effects of fentanyl on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Fentanyl Citrate Injection and any potential adverse effects on the breastfed infant from Fentanyl Citrate Injection or from the underlying maternal condition. Clinical Considerations Monitor infants exposed to fentanyl through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.
Females and Males of Reproductive Potential
Infertility Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions, Clinical Pharmacology, Nonclinical Toxicology].
Pediatric Use
The safety and efficacy of Fentanyl Citrate Injection in pediatric patients under two years of age has not been established. Rare cases of unexplained clinically significant methemoglobinemia have been reported in premature neonates undergoing emergency anesthesia and surgery which included combined use of fentanyl, pancuronium and atropine. A direct cause and effect relationship between the combined use of these drugs and the reported cases of methemoglobinemia has not been established.
Geriatric Use
Elderly patients (aged 65 years or older) may have increased sensitivity to fentanyl. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of Fentanyl Citrate Injection slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions]. Fentanyl is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Hepatic Impairment
Fentanyl Citrate Injection should be administered with caution to patients with liver dysfunction because of the extensive hepatic metabolism. Reduce the dosage as needed and monitor closely for signs of respiratory depression, sedation, and hypotension.
Renal Impairment
Fentanyl Citrate Injection should be administered with caution to patients with kidney dysfunction because of the renal excretion of Fentanyl Citrate Injection and its metabolites. Reduce the dosage as needed and monitor closely for signs of respiratory depression, sedation, and hypotension.
OVERDOSAGE
Clinical Presentation Acute overdose with Fentanyl Citrate Injection can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [See Clinical Pharmacology]. Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measured (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques. The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to fentanyl overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to opioid overdose. Because the duration of opioid reversal is expected to be less than the duration of action of fentanyl in Fentanyl Citrate Injection, carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information. In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be initiated with care and by titration with smaller than usual doses of the antagonist.
mAb BILLING
continued from page 17
Beyond those tips, here are some other steps to consider: • Create a CDM number for each zeropriced drug product as a companion to the regular CDM entry. For example: Drug A 10 mg/mL, CDM number 12345; Drug A, no charge, CDM number 12346. • Create a corresponding PDM entry for these zero-priced drug products and link it to the CDM number. • Meet with your revenue cycle team to learn the quirks of your computerized billing system. • Don’t panic! These billing strategies are used only for a small number of expensive specialty drugs. • When the zero-priced drug product is used, pharmacy must use the order entry for that drug product, not for the purchased product. • Bill for the appropriate CPT inj (injection) drug administration fee(s). • When in doubt, consider CMS’s guidance, which notes that when the drug is zero-priced, the facility/physician should bill the HCPCS code for the drug administered with the correct quantity (according to the dose per unit specified in HCPCS) and a zero charge.
Update on Remdesivir
Switching gears to another important COVID-19–related payment update, on Jan. 7, 2022, CMS released a new HCPCS code for remdesivir (Veklury, Gilead), an antiviral medication indicated for the treatment of adults and pediatric patients 12 years of age and older and weighing 40 kg and over requiring hospitalization for COVID-19. The new code, issued for billing when the antiviral is administered in an outpatient setting, can be used by all payors. The code is effective for dates of service on or after Dec. 23, 2021: • HCPCS code J0248 • Long descriptor: Injection, remdesivir, 1 mg • Short descriptor: Inj, remdesivir, 1 mg
This Year’s Updates to OPPS
Receiving critical payment updates is easy when you’ve signed on to CMS’s MLN Matters distribution list (go. cms.gov/3IoH47F). Although they are electronically provide to the facility’s revenue cycle team, you too can benefit from receiving them. These articles explain national Medicare policy in an easy-to-understand format, and focus on coverage, billing and payment rules for specific provider types. The articles are prepared with help from clinicians, billing experts and CMS subject matter experts, and as we have noted so many times in past columns, are a critical reimbursement resource.
Table. Five New HCPCS Codes
CY 2022 HCPCS Code CY 2022 Long Descriptor CY 2022 SI CY 2022 APCa
A9595 Piflufolastat f-18, diagnostic, 1 millicurie G 9430
C9085 Injection, avalglucosidase alfa-ngpt, 4 mg G 9433
C9086 Injection, anifrolumab-fnia, 1 mg G 9434
C9087 Injection, cyclophosphamide, (Auromedics), 10 mg G 9435
J9021 Injection, asparaginase, recombinant, (Rylaze), 0.1 mg G 9437
a Payment for the drug is for this APC. APC, ambulatory payment classification; CY, calendar year; HCPCS, Healthcare Common Procedure Coding System; SI, status indicator
One of the recent updates detailed in these MLN Matters reports involves multiple changes from the Drugs, Biologicals, and Radiopharmaceuticals section. The changes that are most pertinent to pharmacy are summarized below.
Five new HCPCS codes have been created for reporting passthrough drugs and biologicals in the hospital outpatient setting, where no specific codes were available (effective Jan. 1, 2022) (Table).
HCPCS codes have been established. For more information, see Table 6, Attachment A in CR 12552 (effective Jan. 1, 2022) (go.cms.gov/3Kvg8oB).
Certain vaccines will change retroactively from nonpayable
to payable status in the January 2022 I/OCE Update. See these SI changes for drugs/biologicals in Table 8, Attachment A in CR 12552.
Drugs and biologicals with pay-
ments based on ASP. Several updated payment rates are available in the January 2022 update of the OPPS Addendum A and Addendum B (go. cms.gov/2XA4yl6).
Drugs and biologicals based on
ASP methodology with restated
payment rates. On a quarterly basis, CMS retroactively corrects payment rates for some drugs and biologicals paid based on ASP methodology. The list of drugs and biologicals with corrected payment rates is available on the first date of the quarter; if significant, your facility may resubmit claims that are affected by adjustments to a previous quarter’s payment files. For more information, check out MLN Matters 12552 (go.cms.gov/3GK2Oul).
Physician Fee Schedule Reminder
It’s important to remember that in CY 2020, CMS finalized a policy to apply an amount equal to the site-specific PFS payment rate for non-excepted items and services provided by a non-excepted, off-campus PBD. The agency has completed the phase-in for this payment policy. The PFS-equivalent amount paid to nonexcepted, off-campus PBDs is 40% of the OPPS payment (60% less than the OPPS rate) for CY 2022. Specifically, the total 60% payment reduction will apply in CY 2022. These departments will be paid 40% of the OPPS rate (100% of the OPPS rate minus the 60% payment reduction for the clinic visit service in CY 2022).
For more information on these payment policies, see CMS’s MLN Matters MM12552 document at go.cms. gov/3GK2Oul. Any actions that you can take to mitigate revenue loss and ensure you are telling the patient’s story completely and accurately and in a codable manner will help! ■
A Reimbursement Lexicon
APC, ambulatory payment classification; ASP, average sales price; CDM, charge description master; CMS, Centers for Medicare & Medicaid; CPT, Current Procedural Terminology; CY, calendar year; HCPCS, Healthcare Common Procedure Coding System; IT, information technology; MAC, Medicare administrative contractor; OPPS, Outpatient Prospective Payment System; PBD, provider-based department; PDM, pharmacy drug master; PFS, Physician Fee Schedule
